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==Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid== | ==Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid== | ||
<StructureSection load='5mzc' size='340' side='right' caption='[[5mzc]], [[Resolution|resolution]] 1.82Å' scene=''> | <StructureSection load='5mzc' size='340' side='right'caption='[[5mzc]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5mzc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MZC OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5mzc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MZC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MZC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8EQ:3-(5-CHLORANYL-6-ETHOXY-2-OXIDANYLIDENE-1,3-BENZOXAZOL-3-YL)PROPANOIC+ACID'>8EQ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8EQ:3-(5-CHLORANYL-6-ETHOXY-2-OXIDANYLIDENE-1,3-BENZOXAZOL-3-YL)PROPANOIC+ACID'>8EQ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">kmo, qbsG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Kynurenine_3-monooxygenase Kynurenine 3-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.9 1.14.13.9] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Kynurenine_3-monooxygenase Kynurenine 3-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.9 1.14.13.9] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mzc OCA], [http://pdbe.org/5mzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mzc RCSB], [http://www.ebi.ac.uk/pdbsum/5mzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mzc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5mzc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5mzc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus fluorescens liquefaciens flugge 1886]] | |||
[[Category: Kynurenine 3-monooxygenase]] | [[Category: Kynurenine 3-monooxygenase]] | ||
[[Category: Large Structures]] | |||
[[Category: Rowland, P]] | [[Category: Rowland, P]] | ||
[[Category: Kmo]] | [[Category: Kmo]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 10:33, 19 August 2020
Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acidPseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
Structural highlights
Function[KMO_PSEFL] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin. Publication Abstract from PubMedRecently, we reported a novel role for KMO in the pathogenesis of acute pancreatitis (AP). A number of inhibitors of kynurenine 3-monooxygenase (KMO) have previously been described as potential treatments for neurodegenerative conditions and particularly for Huntington's disease. However, the inhibitors reported to date have insufficient aqueous solubility relative to their cellular potency to be compatible with the intravenous (iv) dosing route required in AP. We have identified and optimized a novel series of high affinity KMO inhibitors with favorable physicochemical properties. The leading example is exquisitely selective, has low clearance in two species, prevents lung and kidney damage in a rat model of acute pancreatitis, and is progressing into preclinical development. Development of a Series of Kynurenine 3-Monooxygenase Inhibitors Leading to a Clinical Candidate for the Treatment of Acute Pancreatitis.,Walker AL, Ancellin N, Beaufils B, Bergeal M, Binnie M, Bouillot A, Clapham D, Denis A, Haslam CP, Holmes DS, Hutchinson JP, Liddle J, McBride A, Mirguet O, Mowat CG, Rowland P, Tiberghien N, Trottet L, Uings I, Webster SP, Zheng X, Mole DJ J Med Chem. 2017 Apr 11. doi: 10.1021/acs.jmedchem.7b00055. PMID:28398044[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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